Isolated tumor cells in the regional lymph nodes in patients with squamous cell carcinoma of the esophagus are rarely observed but often represent part of a true metastasis.

The most common malignancy of the esophagus is squamous cell carcinoma (SCC) and regional lymph node metastases are an important prognostic factor. Isolated tumor cells (ITCs) are defined as single tumor cells or small clusters of tumor cells not exceeding 0.2 mm. The prognostic role of ITCs is not clear. This study aimed to determine the prevalence of ITCs in regional lymph nodes in patients with esophageal SCC and to investigate how frequently ITCs represent part of a true metastasis. Surgical specimens from 100 patients with SCC of the esophagus were included. All original H&E stained slides containing lymph nodes were reviewed by two gastrointestinal pathologists. In lymph nodes containing ITCs, additional levels were cut and stained with a H&E- and a cytokeratin stain. Areas of tumor cells that measured >0.2 mm on the deeper sections were classified as metastases. A total of 2460 lymph nodes were examined. ITCs were detected in 10 lymph nodes (0.4%) from nine patients (9%). Deeper sections revealed metastases in five out of the 10 lymph nodes (50%). ITCs in regional lymph nodes of patients with SCC of the esophagus is a rare finding compared with patients with adenocarcinoma of the esophagogastric junction. However, deeper sections often revealed metastases. Therefore, in patients with SCC of the esophagus, we recommend additional sectioning and immunohistochemical examination of lymph nodes when ITCs are detected on the first slide.

Efficacy of physical examination, ultrasound, and ultrasound combined with fine-needle aspiration for axilla staging of primary breast cancer.

The aim of this study was to compare the efficacy of physical examination (PE), ultrasound (US), and US combined with fine-needle cytology (US-FNAC) in evaluation of node status before sentinel lymph node biopsy (SLNB) for breast cancer patients. We performed a retrospective study of 3,781 breast cancer patients and calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for PE, US, and US-FNAC, respectively. A total of 3,175 cases were documented as cN0 and 606 as cN1. Abnormal axillary nodes under US were detected in 1,152 cases, among which 821 were proven to have positive nodes by FNAC. The positive FNAC results enabled 11.7% of cN0 patients (373/3,175) to avoid unnecessary SLNB. All 331 cases with abnormal US but negative FNAC results, and the 2,629 cases with normal US underwent SLNB procedure for nodal staging, and metastatic nodes were identified in 745 patients. The sensitivity of PE was 32.2%, with a specificity of 95.5%, a PPV of 83.5%, a NPV of 65%, and an accuracy of 69.3%. The sensitivity, specificity, PPV, NPV, and accuracy of axillary US alone were 58.6, 89.4, 79.6, 75.3, and 76.7%, respectively. Combining axillary US with FNAC resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52.4, 100, 100, 74.8, and 80.3%, respectively. Our study demonstrated that US-FNAC is a feasible and effective triage during axillary staging for newly diagnosed breast cancer patients.

Mechanical and structural comparison between primary tumor and lymph node metastasis cells in colorectal cancer.

SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.

Amelanotic melanoma in a New Zealand White Rabbit (Oryctolagus cuniculus).

A 3.5-year-old intact male double-transgenic New Zealand white rabbit (Oryctolagus cuniculus), apoA-I and LCAT (apolipoprotein and lecithin:cholesterol acyltransferase), was presented with a discrete, raised facial mass (0.5 x 1.0 x 1.0 cm). The mass was surgically excised, with reoccurrence to the same site 88 days later. A second surgical excision was performed, and the rabbit died 3 weeks later from respiratory distress. At necropsy, multiple varying-sized masses were observed in the ventral mandibular region and throughout the lungs, pleura, and diaphragm. On histopathology, the masses were composed of moderately anisocytotic and anisokaryotic polygonal to spindloid cells with moderate finely granular, lightly eosinophilic cytoplasm, having round to oval nuclei with one to several nucleoli and finely stippled chromatin. Mitotic figures were frequent. Lymphatic and venous invasion were noted with neoplastic cells metastasized to the submandibular lymph nodes, lungs, liver, and adventitial surface of the aorta. Fontana-Masson stain was negative for melanin, thereby necessitating immunohistochemistry and transmission electron microscopy. Positive staining with MART-1 (a melanocyte protein marker) combined with transmission electron microscopy revealing type II melanosomes confirmed the diagnosis of an amelanotic melanoma.

Carcinoma versus cytokeratin-positive lymphoma: a case report emphasizing the diagnostic role of electron microscopy.

Lymphoma diagnosis rarely needs electron microscopy (EM), but one area where it can be useful is in the distinction of cytokeratin-positive lymphoma from carcinoma. The authors describe such a case, where difficulties were encountered due to lack of antibody specificity, distinguishing reactive from tumoral cells, and suboptimal sampling for EM. The tumor was in a lymph node next to the right submandibular gland in a 69-year-old man. This was a malignant tumor, composed of sheets of monomorphic large round cells. Interpretation on the part of a team of pathologists who examined this tumor was divided. On histological sections, the differential diagnosis was between carcinoma and lymphoma, which was modified to cytokeratin-positive lymphoma versus carcinoma since tumor cells were found to be cytokeratin-positive. EM of tumor retrieved from formalin showed plasmablastic features, in keeping with lymphoma with plasmablastic differentiation, one of the light microscopy diagnoses. The moderately strong positivity of cytokeratin and the positivity for Ber-EP4, however, supported carcinoma, and further sampling for EM was carried out, specifically on a cytokeratin-positive area of the wax block. Tonofibrils were found, supporting carcinoma. The final diagnosis was undifferentiated carcinoma with unknown primary site. The study emphasizes the need to take into account the imperfect specificity of cytokeratin, which can be found in several hemolymphoid neoplasms, to distinguish reactive from neoplastic cells, and to secure appropriate sampling for EM. This is one of the occasions where dewaxing (of an immunohistochemically defined wax block) offers positive advantages, despite compromised structural preservation, in the search for diagnostically important organelles.

[Lymph node image with ultrasmall superparamagnetic iron oxide and comparison with pathological result].

OBJECTIVE: To assess the characteristics of enhanced magnetic resonance image with ultrasmall superparamagnetic iron oxide (USPIO) in the inflammatory and tumor metastatic rabbit model, and explore its relevance with histologic ultrastructural findings. METHODS: Totally 36 New Zealand white rabbits were randomly divided into lymphadenitis group and metastatic group. Complete Freund's adjuvant was injected into the bilateral dorsal footpads of 18 rabbits to set up ipsilateral lymphadenitis model. The other 18 rabbits received a subcutaneous implantation of VX2 tumor cell suspension (1.5 x 10(7) cells/ml) in both thighs to set up metastatic lymph node model. Magnetic resonance scan were performed 24 hours before and after USPIO (90 micromol Fe/kg) injection. T2 values of each lymph node were measured and lymph node T2 enhancement rate was calculated as well. HE staining, Prussian blue staining, and electronic microscopy were performed to observe the pathological microstructure changes and the distribution of the iron particle in lymph node. Relationship between lymph nodes USPIO enhancement and its microstructures were further analyzed. Results Thirty-six lymph nodes in lymphadenitis group showed different degrees of reactive hyperplasia. Twenty-six lymph nodes in metastatic group were invaded by tumor cell. Non-enhanced scan showed mild difference between T2 signal intensity of the two pathological lymph node types. After USPIO enhancement, inflammatory lymph nodes showed distinct T2 signal reduction at the center, and metastatic lymph nodes showed homogenous and faint T2 signal reduction. Enhancement rate of benign and malignant lymph nodes were 57.39% and 29.45% respectively (P < 0.01). HE staining and Prussian blue staining indicated USPIO particles located mainly in the macrophages at inflammatory lymphatic medulla, while paracortical area and cortical area contained relatively much less USPIO particles due to less macrophages distribution. MRI findings were correlated with the pathological results. Electronic microscopy also verified that the majority of USPIO particles were located in the numerous cytophagic bubbles of macrophages. Lymph nodes metastasis including 4 lymph nodes with completed structure destruction due to entire tumor infiltration, 19 lymph nodes with partially lymph node structure destruction but reduced USPIO-contained macrophage numbers or reduced USPIO particles in macrophages, and 3 lymph nodes with only localized foci tumor metastasis at subcapsular area. Conclusions USPIO enhancement pattern of different lymph nodes is closely related to distribution and functional status of the intra-node macrophages. It may affect the accuracy of the lymph node property diagnosis based on USPIO enhanced image.

The potential of nanoparticle-enhanced imaging.

Accurate lymph node staging in genitourinary malignancy is an important component in the diagnostic algorithm and therapeutic planning. A promising new method for lymph node staging is lymphotrophic nanoparticle enhanced magnetic resonance imaging. This novel technique uses ultrasmall superparamagnetic iron oxide particles, which localize in lymph nodes and provide detailed characterization of these nodes independent of typically accepted size criteria. This review provides a brief overview of the presently accepted methods for noninvasive lymph node staging and thoroughly discusses lymphotrophic nanoparticle enhanced MR imaging: a technique that can be used for accurate detection of lymph node metastases and will likely play a major role in noninvasive lymph node staging in genitourinary cancer in the near future.

Sentinel lymph node biopsy for melanoma: aspects of pathologic assessment.

Sentinel lymph node (SLN) biopsy affords an accurate, minimally invasive means of staging and determining prognosis in patients with melanoma and for identifying those patients who may benefit from complete regional lymph node dissection. Careful and accurate histopathologic assessment of SLNs is critical to achieving optimal reliability of the technique. Micromorphometric parameters of melanoma deposits in SLNs have been shown to be predictive of regional non-SLN involvement and of clinical outcomes. Several non-histopathologic methods of SLN evaluation have been investigated, and while some of them show promise for the future, excision and histopathologic examination currently remains the gold standard for the evaluation of SLNs.

Mechanisms of invasion and lymphatic penetration in human colorectal cancer.

The invasive areas in 24 unselected human colorectal cancers were examined by light and electron microscopy and it was shown that the invasive process involves tubes of cells rather than single cells, that degenerative changes take place in specialized cells ahead of the invasive cancer cells and that the endothelium of the lymphatic vessels disintegrates, leaving gaps in the endothelial lining.

Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus).

We report on the clinical and pathologic features of 32 lesions diagnosed as malignant spindle cell and epithelioid cell nevus (S&E nevus). Because of the clinical or initial histopathologic diagnosis of malignant melanoma, six patients had lymph node dissection. Three of these patients also had an enlarged lymph node. In all six cases, metastatic spindle or epithelioid cells were found in at least one of the resected lymph nodes. Of the 30 patients with follow-up information, including all six patients with lymph node metastases, all are alive and well. No recurrences or further metastases have been found. On histopathologic reevaluation, all the lesions had features of S&E nevi. Study of these cases suggests that although some lesions with features of S&E nevi may involve local lymph nodes, widespread metastases do not result.

Primary pulmonary paraganglioma: report of a functioning case with immunohistochemical and ultrastructural study.

We describe a case of primary pulmonary paraganglioma, a tumor that has not been reported in sufficient detail in previous literature. The patient was a 55-year-old woman with hypertension accompanied by an elevated serum norepinephrine level (2651 pg/mL; normal 100-450 pg/mL). Computed tomography revealed a well-circumscribed solid mass, 3.5 cm in diameter, located in the lower lobe of the left lung. In the lobectomy specimen, the tumor had invaded the B8 bronchus and hilar lymph nodes with microscopic metastasis to the mediastinal nodes. The tumor showed histologic, immunohistochemical, and ultrastructural features of paraganglioma: argyrophilic cells arranged in a nesting (Zellballen) or anastomosing trabecular pattern within an arcuate vascular network. Neoplastic chief cells positive for neuroendocrine markers (CD56, synaptophysin, chromogranin A) were surrounded by sustentacular cells positive for S-100 protein. Neurofilament protein was positively stained, but cytokeratins were totally negative. On electron microscopy, chief cells possessed abundant dense core granules with an eccentric halo ("norepinephrine-type" granules). The patient's blood pressure began to decline soon after the resection, and her serum norepinephrine promptly returned to almost normal. On the basis of our experience, our case is a bona fide primary pulmonary paraganglioma, a tumor heretofore subject to considerable skepticism.

Lymph node metastasis as the initial manifestation of malignant mesothelioma. Report of six cases.

We present six cases in which lymphadenopathy was the initial manifestation of malignant mesothelioma. In five cases, the primary tumor was located in the peritoneum; it was located in the pleura in the sixth. The involved lymph nodes were cervical in four cases, mediastinal in one, and inguinal in one. The morphologic, immunohistochemical, and ultrastructural features were typical of malignant epithelial mesothelioma. A review of the literature disclosed only one previously documented example of this phenomenon. When confronted with a lymph node involved by metastatic tumor, pathologists should be aware that malignant mesothelioma can present initially in the form of lymphadenopathy and include this possibility in the differential diagnosis.

Fine structure of three major grades of malignancy of human pancreatic adenocarcinoma.

Fine structural analysis of a series of 51 adenocarcinoma in the human pancreas revealed their composition of one major cell type, a mucoprotein secreting cell which has a number of structural features resembling the cells of the larger interlobular ducts in the normal pancreas. In addition to mucus secretion, the tumor cells released large quantities of membrane material, both as vesicles pinched off from microvilli and as blebs sequestered from the plasma membrane. At the ultrastructural level the subdivision of tumors into three major grades of malignancy was manifested by a progressive loss in cell polarity and a reduction in the association of tumor cells with elements of the extracellular matrix (basal lamina). The highest grade of differentiation grew as tubular structures with a common luminal space, while with progressive dedifferentiation and loss of cell polarity secretion occurred into both luminal and interstitial spaces. This release pattern of tumor cell products, which constitute a complex mixture of exportable and constitutive proteins, will lead to their appearance in both pancreatic juice and blood circulation. Tumor cell spreading occurred along perineural sheaths and was combined with nerve fiber destruction. Primary tumors and lymph node or liver metastases did not differ significantly in their respective grading.

Upper gastrointestinal bleeding due to a malignant Schwannoma of the stomach.

A case history of a patient showing signs of upper gastrointestinal bleeding is described. Extensive analysis showed that the bleeding was due to a malignant Schwannoma of the stomach with several lymph node metastases. The patient was operated on and is doing well 5 years after surgery. The literature on this rare malignant tumour is reviewed.

Nuclear morphometry and stereology in nasopharyngeal carcinoma.

The prognostic value of nuclear morphometry in nasopharyngeal carcinoma (NPC) was investigated in 28 patients. Seven morphometric nuclear variables were measured on 100 randomly selected tumor cells in nasopharyngeal biopsies from 18 patients with NPC confined to the nasopharynx. The same variables were measured in 6 patients with metastatic NPC, as well as in lymph node biopsies from 4 patients with metastatic NPC. Nuclear area, nuclear perimeter, long and short nuclear axes, nuclear form factor, nucleolar area, and the ratio of nucleolar area to nuclear area were all measured. Volume-weighted mean nuclear volume was also obtained. Tumor cells from patients with NPC confined to the nasopharynx had significantly larger mean nuclear areas, perimeters, and volume-weighted mean nuclear volumes but significantly smaller nucleolar to nuclear area ratios than tumor cells from patients with nodal metastases. Assessment of nuclear form factor and diameters did not differentiate the two groups.

Epithelial inclusion in axillary lymph node associated with a breast carcinoma: report of a case with a review of the literature.

Since epithelial inclusions in axillary lymph nodes are rare, some diagnostic problems concerning their nature have arisen. We report a case of a cystic squamous epithelial inclusion in an axillary lymph node of a patient affected by a high grade breast carcinoma with focal squamous differentiation. Although the lesion was histologically benign, the possibility that it represents a well-differentiated squamous metastasis cannot be completely ruled out. To our knowledge, this is the first case of an epithelial lymph node inclusion associated with a breast carcinoma showing morphological evidence of squamous differentiation. Here, we discuss the diagnostic problems and give a review of the literature.

Immunoreactive calcitonin in amyloid fibrils of medullary carcinoma of the thyroid gland. An immunogold staining technique.

A lymph node containing metastatic medullary carcinoma of the thyroid gland was examined immunohistochemically for the presence of calcitonin by light and electron microscopy. Electron microscopy showed dense, selective labeling of the tumor-associated amyloid fibrils and labeling of the scanty intracytoplasmic neurosecretory granules. By light microscopy, a few tumor cells showed strong staining, whereas the amyloid fibrils showed equivocal staining.

Presence of nuclear grooves in the cytology of malignant melanoma.

Nuclear grooves have been described as a cytologic feature in a variety of extrathyroid lesions. When a cytologic specimen demonstrates prominent longitudinal nuclear grooving, a wide range of pathologic lesions should be considered. To our knowledge, the two cases presented are the first report of longitudinal nuclear grooving described in cytologic preparations of malignant melanoma.

Signet-ring cell melanoma mimicking adenocarcinoma. A case report.

The fine needle aspiration findings in a lymph node involved by signet-ring cell melanoma, a very rare variant of malignant melanoma, are reported. The patient had a history of superficial spreading melanoma of the right foot, treated 10 years earlier by below-the-knee amputation. He presented with a right groin mass. Fine needle aspiration of the mass yielded poorly cohesive, large cells with eccentric nuclei and abundant, eosinophilic cytoplasm; many of them exhibited a signet-ring appearance. Melanin pigments were identified in a small proportion of tumor cells, and a diagnosis of metastatic melanoma was made. The subsequent lymph node excision revealed a metastatic tumor composed of polygonal and signet-ring cells that were positive for S-100 protein and HMB-45 but not cytokeratin. Nearly all reported cases of signet-ring cell melanoma occurred as metastatic or recurrent disease. It is important not to mistake signet-ring cell melanoma for adenocarcinoma in aspiration cytology, and a constellation of clinical features and of histochemical and immunohistochemical findings enables a correct diagnosis to be reached.

[Aneuploidia in malignant tumors of testis and their lymphatic metastases (author's transl)]. / Aneuploidie bei malignen Hodentumoren und ihren Lymphknotenmetastasen.

DNA-estimations, done by flow-through-cytophotometry, were performed in 18 malignant tumors of testis. Aneuploid stemlines which are specific for cancers were found in 17 cases. The only exception was a so called "occult seminoma". It showed only a small difference between the stem-line of tumor and normal cells of testis. So, by using DNA-estimation, it was possible to make a correct diagnosis all 18 patients, suffering from tumor of the testis. The aneuploid stem-lines of seminomas did not differ from those of other cancers. The type of proliferative behavior seems to be a criterion for prognosis. Lymphatic nodes with and without formation of metastases very clearly showed differences in the DNA-content of their nuclei.